Role of the vasodilator peptide angiotensin-(1-7) in cardiovascular drug therapy

Abstract

The renin-angiotensin-system (RAS) is a cascade of enzymatic reactions resulting ultimately in the formation of angiotensin II. Recent research has expanded the knowledge about the RAS by adding new components to the pathways: angiotensin-(1-5) [Ang-1-5], angiotensin-(1-7) [Ang-(1-7)], angiotensin-(1-9) [Ang-(1-9)], an ACE homologous enzyme, ACE2, and the G-protein-coupled receptor mas as a molecular receptor for Ang-(1-7). Although previous studies provided some conflicting evidence about the relevance of Ang-(1-7) in the regulation of vascular and renal function, data now demonstrate that Ang-(1-7) contributes to the cardiovascular effects of ACE-inhibitors (ACE-1) and AT1-receptor-blockers (ARBs) both in experimental conditions and in humans. This review summarizes and critically discusses the currently available experimental and clinical study evidence for the role of Ang-(1-7) as a vasodilator and anti-trophic peptide in cardiovascular drug therapy. In addition, the potential therapeutic impact of currently available RAS blocking agents (ACE-1 and ARBs) and new agents still under development (renin-inhibitors) on the RAS-effector peptides is highlighted.

Figure 1

Pathways for the formation of biologically active angiotensin peptides. Abbreviations: ACE, angiotensin-converting enzyme; ACE2, ACE-related carboxypeptidase; CBP, carboxypeptidase; BK, bradykinine; CBP, carboxypeptidase; EDRF, endothelium derived relaxing factor; NEP, neutral endopeptidase; NO, nitric oxide; PEP, prolylendopetidase; PKG, proteine kinase G.

Figure 2

Systematic overview of angiotensinogen (its crucial n-terminal part), angiotensin I, angiotensin II, and angiotensin-(1-7) with sites of enzymatic cleavage.